Transport of thyroxine and 3,3',5-triiodothyronine in human umbilical vein endothelial cells.
The prerequisite for the uptake of thyroid hormone (TH) in peripheral tissues is the exit of TH from the bloodstream. The first step in this process is transport across the endothelium. Little is known about this important step in TH physiology. Therefore, we aimed to characterize the TH transport processes across the endothelium using human umbilical vein endothelial cells as a model. Transport studies showed rapid uptake of 1 nm [(125)I]T(3) and [(125)I]T(4) in these cells. The apparent Michaelis constant value for [(125)I]T(3) uptake was about 1 microm, and the IC(50) for T(4) inhibition of T(3) uptake was about 3 microm. The aromatic amino acids phenylalanine, tyrosine, and tryptophan and the L-type amino acid transporter-specific ligand 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid did not inhibit [(125)I]T(3) or [(125)I]T(4) uptake. Verapamil was capable of reversibly reducing transport of [(125)I]T(3) and [(125)I]T(4). Human umbilical vein endothelial cells incubated with the affinity label BrAcT(3) resulted in a labeling of multiple proteins, which are probably protein disulfide isomerase related. Extrapolating our findings to the endothelial lining of blood vessels suggests that T(3) and T(4) uptake is mediated by the same transport system. Because TH transport characteristics do not correspond to known TH transporters, further studies are required to identify the TH transporter protein(s) at the molecular level. Possible candidates may be widely expressed Na(+)-independent transporter proteins.
Visser
W Edward
WE
Department of Internal Medicine, Erasmus University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. t.j.visser@erasmusmc.nl.
Friesema
Edith C H
EC
Visser
Theo J
TJ
D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D001692:Biological Transport; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D027981:Symporters; D013974:Thyroxine / Q000378:metabolism*; D014285:Triiodothyronine, Reverse / Q000378:metabolism* / Q000493:pharmacokinetics; D014471:Umbilical Veins / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D026921:Amino Acid Transport Systems, Neutral; D007457:Iodine Radioisotopes; D027501:Monocarboxylic Acid Transporters; C498964:SLC16A10 protein, human; C090735:SLC16A2 protein, human; D027981:Symporters; D014665:Vasodilator Agents; D014285:Triiodothyronine, Reverse; D014700:Verapamil; D013974:Thyroxine